The present invention relates to the use of certain deazapurine nucleoside analogs in the treatment of viral infections. More particularly, the present invention relates to the use of certain pyrrolo2,3-d!pyrimidine nucleoside analogs against human cytomegalovirus and herpes simplex virus type 1.
Broad spectrum antiviral activity of pyrrolo2,3-d!pyrimidine nucleosides such as tubercidin, sangivamycin and toyocamycin and some substituted derivatives has been previously reported. Activity of those compounds against specific viruses, such as RNA rhinovirus and DNA herpes simplex virus type 1 and type 2 has also been reported. See, for example, Bergstrom, D. E. et al., J. Med. Chem., 27: 285-292 (1984); and DeClercq, E. et al., Antimicrob. Agents Chemother., 29:482-487 (1986).
Pyrrolo2,3-!pyrimidine nucleosides are particularly attractive as potential antiviral agents because of their stability toward the two major pathways of bioactive purine nucleoside inactivation, deamination by adenosine deaminase and glycosidic bond cleavage by purine nucleoside phosphorylases. Unfortunately, pyrrolo2,3-d!pyrimidine nucleosides which have been previously described as potently antiviral also exhibit unacceptable levels of cytotoxicity, thereby diminishing their usefulness in treatment of viral infections in animals.
It would thus be very desirable to discover derivatives of these compounds having decreased cytotoxicity while retaining their antiviral properties. Such a discovery has been made and is the basis for the present invention which relates to a class of 4, 5, 6, 7-substituted pyrrolo2,3-d!pyrimidine analogs which exhibit levels of cytotoxicity significantly lower than their parent compounds, yet retain antiviral activity, particularly against DNA human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1).